Submissions for variant NM_000397.4(CYBB):c.1165G>A (p.Gly389Arg)

dbSNP: rs1556471150

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589173	SCV000696681	uncertain significance	not provided	2016-05-12	criteria provided, single submitter	clinical testing	Variant summary: The CYBB c.1165G>A (p.Gly389Arg) variant involves the alteration of a conserved nucleotide, resulting in a missense change from a non-polar Gly to a positively charged Arg residue. Gly389 is a highly conserved amino acid across species located in the dehydrogenase domain of the protein. This variant is located in a mutation hotspot since missense changes at this residue have been cited in multiple X-CGD patients, indicating that missense changes at this residue are not tolerated. 5/5 in silico tools predict a damaging outcome for this variant. Functional studies of other missense changes at Gly389 have been shown to abolish NADPH oxidase activity (Beaumel_Biochem Journal_2014). This variant was absent in 86756 control chromosomes, but has been cited in one patient in CYBB base. Because of the limited clinical information and the lack of functional studies on this particular missense variant, the variant was classified as a variant of uncertain significance (VUS)-possibly pathogenic until additional information becomes available.
Clinic of Clinical Immunology with Stem Cell Bank, Expert Centre for Rare Diseases - PID, University Hospital "Alexandrovska"	RCV002283491	SCV002573419	likely pathogenic	Granulomatous disease, chronic, X-linked	2022-05-01	no assertion criteria provided	clinical testing